WO2015197698A3 - Verfahren zur biokatalytischen ganzzellreduktion von dehydrocholsäureverbindungen, sowie 7beta-hydroxysteroid dehydrogenase-mutanten - Google Patents

Verfahren zur biokatalytischen ganzzellreduktion von dehydrocholsäureverbindungen, sowie 7beta-hydroxysteroid dehydrogenase-mutanten Download PDF

Info

Publication number
WO2015197698A3
WO2015197698A3 PCT/EP2015/064264 EP2015064264W WO2015197698A3 WO 2015197698 A3 WO2015197698 A3 WO 2015197698A3 EP 2015064264 W EP2015064264 W EP 2015064264W WO 2015197698 A3 WO2015197698 A3 WO 2015197698A3
Authority
WO
WIPO (PCT)
Prior art keywords
hydroxysteroid dehydrogenase
biocatalytic
whole cell
beta
acid compounds
Prior art date
Application number
PCT/EP2015/064264
Other languages
English (en)
French (fr)
Other versions
WO2015197698A2 (de
Inventor
Dirk Weuster-Botz
Boqiao Sun
Christian QUIRIN
Original Assignee
Pharmazell Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pharmazell Gmbh filed Critical Pharmazell Gmbh
Priority to JP2016569760A priority Critical patent/JP6666855B2/ja
Priority to US15/314,155 priority patent/US10544441B2/en
Priority to EP15731902.1A priority patent/EP3161144B1/de
Priority to NZ725965A priority patent/NZ725965A/en
Priority to KR1020177001891A priority patent/KR102640531B1/ko
Publication of WO2015197698A2 publication Critical patent/WO2015197698A2/de
Publication of WO2015197698A3 publication Critical patent/WO2015197698A3/de

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P33/00—Preparation of steroids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/70—Vectors or expression systems specially adapted for E. coli
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
    • C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
    • C12Y101/01047—Glucose 1-dehydrogenase (1.1.1.47)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
    • C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
    • C12Y101/0105—3Alpha-hydroxysteroid 3-dehydrogenase (B-specific) (1.1.1.50)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
    • C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
    • C12Y101/01145—3-Beta-hydroxy-DELTA5-steroid dehydrogenase (1.1.1.145)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
    • C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
    • C12Y101/01201—7-Beta-hydroxysteroid dehydrogenase (NADP+) (1.1.1.201)

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Steroid Compounds (AREA)

Abstract

Die Erfindung betrifft neuartige biokatalytische Prozesse, umfassend die Ganzzell-Reduktion von Dehydrocholsäure(DHCS)-Verbindungen, neuartige 7ß-Hydroxysteroid Dehydrogenase-Mutanten, die für diese Enzym-Mutanten kodierenden Sequenzen, Verfahren zur Herstellung der Enzym-Mutanten und deren Verwendung bei enzymatischen Umsetzungen von Cholsäureverbindungen, und insbesondere bei der Herstellung von Ursodesoxycholsäure (UDCS); Gegenstand der Erfindung sind auch neuartige Verfahren zur Synthese von UDCS unter Verwendung der Enzym-Mutanten; sowie insbesondere ein weiter verbessertes Verfahren zur Herstellung von UDCS unter Verwendung rekombinanter Ganzzell-Biokatalysatoren.
PCT/EP2015/064264 2014-06-24 2015-06-24 NEUARTIGE VERFAHREN ZUR BIOKATALYTISCHEN GANZZELLREDUKTION VON DEHYDROCHOLSÄUREVERBINDUNGEN, NEUARTIGE 7ß-HYDROXYSTEROID DEHYDROGENASE-MUTANTEN UND VERBESSERTE BIOKATALYTISCHE VERFAHREN ZUR HERSTELLUNG VON URSODESOXYCHOLSÄURE WO2015197698A2 (de)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP2016569760A JP6666855B2 (ja) 2014-06-24 2015-06-24 デヒドロコール酸化合物の生体触媒ホールセル還元のための新規方法、新規７β−ヒドロキシステロイドデヒドロゲナーゼ変異体、およびウルソデオキシコール酸を産生するための改良された生体触媒法
US15/314,155 US10544441B2 (en) 2014-06-24 2015-06-24 Method for biocatalytic whole cell reduction of dehydrocholic acid compounds, and 7-β-hydroxysteroid dehydrogenase mutants
EP15731902.1A EP3161144B1 (de) 2014-06-24 2015-06-24 Verfahren zur biokatalytischen ganzzellreduktion von dehydrocholsäureverbindungen, sowie 7beta-hydroxysteroid dehydrogenase-mutanten
NZ725965A NZ725965A (en) 2014-06-24 2015-06-24 Method for biocatalytic whole cell reduction of dehydrocholic acid compounds, and 7-beta-hydroxysteroid dehydrogenase mutants
KR1020177001891A KR102640531B1 (ko) 2014-06-24 2015-06-24 디하이드로콜린산 화합물의 생체촉매적 전세포 환원을 위한 방법, 7β-히드록시스테로이드 탈수소효소 변이체들 및 우르소데스옥시콜린산을 제조하기 위한 개선된 생체촉매 방법

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP14173747 2014-06-24
EP14173747.8 2014-06-24
EP14182290.8 2014-08-26
EP14182290 2014-08-26

Publications (2)

Publication Number Publication Date
WO2015197698A2 WO2015197698A2 (de) 2015-12-30
WO2015197698A3 true WO2015197698A3 (de) 2016-02-25

Family

ID=53489945

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2015/064264 WO2015197698A2 (de) 2014-06-24 2015-06-24 NEUARTIGE VERFAHREN ZUR BIOKATALYTISCHEN GANZZELLREDUKTION VON DEHYDROCHOLSÄUREVERBINDUNGEN, NEUARTIGE 7ß-HYDROXYSTEROID DEHYDROGENASE-MUTANTEN UND VERBESSERTE BIOKATALYTISCHE VERFAHREN ZUR HERSTELLUNG VON URSODESOXYCHOLSÄURE

Country Status (7)

Country Link
US (1) US10544441B2 (de)
EP (1) EP3161144B1 (de)
JP (1) JP6666855B2 (de)
KR (1) KR102640531B1 (de)
NZ (1) NZ725965A (de)
PT (1) PT3161144T (de)
WO (1) WO2015197698A2 (de)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110387360B (zh) * 2019-06-18 2021-12-28 华东理工大学 羟基类固醇脱氢酶及其在合成熊去氧胆酸前体中的应用

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7035034B2 (ja) 2016-06-20 2022-03-14 ファルマツェル、ゲーエムベーハー ケノデオキシコール酸のウルソデオキシコール酸への共役自己完結型（ｓｅｌｆ－ｓｕｆｆｉｃｉｅｎｔ）生体内変換および前記方法において適用可能な新規酵素突然変異体
WO2018036982A1 (de) 2016-08-22 2018-03-01 Pharmazell Gmbh Chemisch-biokatalytisches verfahren zur herstellung von ursodesoxycholsäure
CN107980060B (zh) * 2017-01-09 2021-05-25 深圳市邦泰绿色生物合成研究院 一种3α-羟基-7氧代-5β-胆烷酸的制备方法及其制备用酶2
NL2020823B1 (en) * 2018-04-25 2019-11-05 Univ Delft Tech NAD+ dependent 7ß-hydroxysteroid dehydrogenase
CN113968891B (zh) * 2021-11-15 2023-04-07 湖南科瑞生物制药股份有限公司 一种植物源7-酮基石胆酸的制备方法
CN115386557A (zh) * 2022-10-14 2022-11-25 安徽大学 一种7α-羟基类固醇脱氢酶的制备方法及其催化转化应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012080504A1 (de) * 2010-12-16 2012-06-21 Pharmazell Gmbh NEUARTIGE 7ß-HYDROXYSTEROID DEHYDROGENASE-MUTANTEN UND VERFAHREN ZUR HERSTELLUNG VON URSODESOXYCHOLSÄURE

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5651997A (en) * 1979-10-05 1981-05-09 Toyobo Co Ltd Preparation of 12-keto cheno deoxycholic acid by microorganism
US6675479B1 (en) 2000-02-29 2004-01-13 The Gillette Company Shaving razor and blade unit with improved guard
EP2105500A1 (de) 2008-03-26 2009-09-30 Pharmazell GmbH Neue 12alpha-Hydroxysteroiddehydrogenasen, deren Herstellung und deren Verwendung
CN105936897A (zh) * 2009-11-30 2016-09-14 细胞制药有限公司 新的7β-羟类固醇脱氢酶及它们的用途

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012080504A1 (de) * 2010-12-16 2012-06-21 Pharmazell Gmbh NEUARTIGE 7ß-HYDROXYSTEROID DEHYDROGENASE-MUTANTEN UND VERFAHREN ZUR HERSTELLUNG VON URSODESOXYCHOLSÄURE

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BOQIAO SUN ET AL: "Multi-enzymatic one-pot reduction of dehydrocholic acid to 12-keto-ursodeoxycholic acid with whole-cell biocatalysts", BIOTECHNOLOGY AND BIOENGINEERING, vol. 110, no. 1, 18 January 2013 (2013-01-18), pages 68 - 77, XP055169454, ISSN: 0006-3592, DOI: 10.1002/bit.24606 *
H.-J. MOON ET AL: "Molecular Determinants of the Cofactor Specificity of Ribitol Dehydrogenase, a Short-Chain Dehydrogenase/Reductase", APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 78, no. 9, 17 February 2012 (2012-02-17), US, pages 3079 - 3086, XP055233711, ISSN: 0099-2240, DOI: 10.1128/AEM.07751-11 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110387360B (zh) * 2019-06-18 2021-12-28 华东理工大学 羟基类固醇脱氢酶及其在合成熊去氧胆酸前体中的应用

Also Published As

Publication number Publication date
JP2017522006A (ja) 2017-08-10
US20170191104A1 (en) 2017-07-06
EP3161144B1 (de) 2019-09-18
WO2015197698A2 (de) 2015-12-30
EP3161144A2 (de) 2017-05-03
KR102640531B1 (ko) 2024-02-23
JP6666855B2 (ja) 2020-03-18
US10544441B2 (en) 2020-01-28
PT3161144T (pt) 2019-12-18
KR20170020511A (ko) 2017-02-22
NZ725965A (en) 2022-04-29

Similar Documents

Publication Publication Date Title
WO2015197698A3 (de) Verfahren zur biokatalytischen ganzzellreduktion von dehydrocholsäureverbindungen, sowie 7beta-hydroxysteroid dehydrogenase-mutanten
AU2011343222B2 (en) Novel 7B-hydroxysteroid dehydrogenase mutants and process for the preparation of ursodeoxycholic acid
WO2009125924A3 (ko) 퓨트레신 고생성능을 가지는 변이 미생물 및 이를 이용한 퓨트레신의 제조방법
WO2018124440A3 (ko) 신규한 이소프로필말레이트 신타제 변이체 및 이를 이용한 l-류신의 생산 방법
WO2011126897A3 (en) Methods for enhancing by-products from fermentation processes
WO2010104390A3 (en) Preparation of alpha-ketopimelic acid
WO2011061032A3 (de) Zellen, nukleinsäuren, enzyme und deren verwendung sowie verfahren zur herstellung von sophorolipiden
WO2012173659A3 (en) Lignocellulosic hydrolysates as feedstocks for isobutanol fermentation
EP2558584A4 (de) Verfahren zur herstellung von gärungsprodukten
WO2009081012A3 (fr) Procedes de production d'acide succinique
WO2013105802A3 (ko) 자일로즈 이용능이 부여된 코리네박테리움 속 미생물 및 이를 이용한 ｌ-라이신의 생산방법
PH12019501001A1 (en) Method for preparing electrocompetent yeast cells, and method for using said cells
WO2016071505A9 (en) Microbial production of the flavonoids garbanzol, resokaempferol and fisetin
EP3272860A4 (de) Pyruvat-dehydrogenase-mutant, mikroorganismus mit dem mutanten sowie verfahren zur herstellung von l-aminosäure mit dem mikroorganismus
MY189932A (en) Recombinant microorganism for improved production of alanine
WO2018203947A3 (en) MODIFIED BIOSYNTHESIS PATHWAYS FOR FERMENTATION TYRAMINE PRODUCTION
UA108343C2 (uk) Спосіб одержання сквалену за допомогою дріжджів
EP2612905A4 (de) Neuer mutanter mikroorganismus zur herstellung von bernsteinsäure unter gleichzeitiger verwendung von saccharose sowie verfahren zur herstellung von bernsteinsäure damit
EP4039796A4 (de) Verfahren zur herstellung einer zusammensetzung für die zellkultivierung, dadurch hergestellte zusammensetzung für die zellkultivierung und zellkultivierungsverfahren damit
PH12019500096A1 (en) Leuconostoc mesenteroides cjlm119 strain producing reduced amount of gas, and kimchi production method using same
EP3666900A3 (de) Zellbasierte herstellung von nonulosonaten
WO2013064682A3 (en) Fermentation process for producing chemicals
MY176164A (en) Means and methods for the enzymatic production of l--methionine from o-phospho-l-homoserine and methanethiol
MY188314A (en) Fermentation process with improved glycerol and acetic acid conversion
MX2021006808A (es) Novedosa psicosa-6-fosfato fosfatasa, composicion para la produccion de psicosa que comprende la misma y procedimiento para la produccion de psicosa mediante el uso de la misma.

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15731902

Country of ref document: EP

Kind code of ref document: A2

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
ENP Entry into the national phase

Ref document number: 2016569760

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 15314155

Country of ref document: US

REEP Request for entry into the european phase

Ref document number: 2015731902

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2015731902

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 20177001891

Country of ref document: KR

Kind code of ref document: A